Accelerating Typhoid Conjugate Vaccine Introduction: What Can Be Learned From Prior New Vaccine Introduction Initiatives?

"Accelerated vaccine introduction requires a strong human component to ensure the necessary relationships and data exchange between global, regional, and local entities, to include policymakers, vaccine developers, researchers, and clinicians."

Since 2000, large-scale initiatives have accelerated a number of vaccine introductions into low-resource populations at the national, regional, and global scales. Each vaccine introduction is a complex and unique process. Informed by prior successful vaccine introductions, the Typhoid Vaccine Acceleration Consortium (TyVAC) employs an integrated, proactive approach in countries eligible for support from Gavi, the Vaccine Alliance, that is tailored to the nuances of typhoid disease and the typhoid conjugate vaccine (TCV). TyVAC is conducting clinical efficacy trials in Bangladesh, Nepal, and Malawi, to provide data in diverse settings on vaccine impact against a number of relevant outcomes. The iterative process detailed herein summarises the strategy and experience gained from the first 2 years of the project.

Figure 1 (see above) illustrates the key components of new vaccine introduction, featuring feedback loops at every step, and provides a strategic framework for TyVAC. Data are continually generated, processed, shared, and acted upon by international, national, and local stakeholders. The required components of successful vaccine introductions in low-resource countries are shown in blue boxes, and the interrelationships between stakeholders are shown in the white boxes and with arrows. Previous successful vaccine introduction programmes have emphasised the importance of coordination and advocacy and communication across all stages and between stakeholders.

TyVAC's framework of vaccine introduction took into account challenges and data gaps from historical vaccine introduction initiatives. Examples of lessons learned include:

• The Meningitis Vaccine Project (MVP) developed, tested, licensed, and introduced MenAfriVac, a group A meningococcal conjugate vaccine, designed for populations in sub-Saharan Africa. A unique challenge facing MVP was the fact that the available multivalent vaccines were not affordable. The project success was attributed to country and regional engagement, a rigorous clinical development plan, a strategic introduction plan, and key partnerships between countries, international organisations, and the vaccine developer. MenAfriVac was prequalified by the World Health Organization (WHO) in June 2010 and introduced the same year. By 2017, more than 280 million Africans had been vaccinated.
• One of the elements of the Japanese encephalitis (JE) Project was establishing good cross-country, regional communication. Subsequently, the JE Project identified an appropriate vaccine for low-income countries, worked with a developing-country vaccine manufacturer to obtain WHO prequalification and supply the vaccine, and formed key partnerships with WHO, Gavi, and the United Nations Children's Fund (UNICEF).
• The Haemophilus influenzae type b (Hib) Initiative leadership recognised that the lack of awareness and data on disease burden, particularly in Asia, was hampering vaccine introduction. Clear communication about disease burden, financing, and vaccine supply helped accelerate decision making and generate a sense of urgency to support introduction. By the end of 2017, Hib vaccine had been introduced in 191 countries.
• The Pneumococcal Vaccines Accelerated Development and Introduction Plan (PneumoADIP) was designed to address supply and demand issues thought to hinder previous vaccine introductions. The project used a 3-pronged approach of surveillance and research, advocacy and communication (A&C), and vaccine supply and financing. For example, A&C efforts brought the importance of pneumonia in under-5 mortality to policymakers, political leaders, and donors. By the end of 2017, the estimated global coverage was 44% with pneumococcal vaccine introduced in 136 countries.
• In 2006, while rotavirus vaccines were licensed and available in high-resource countries, there was no WHO recommendation for use in low-resource settings. The Rotavirus Vaccine Project (RVP) emphasised the importance of stakeholder involvement, unifying and clear communications, logistical feasibility, and political will. To accelerate vaccine introduction, the Rotavirus Accelerated Vaccine Introduction Network was formed in 2016. As of August 2018, rotavirus vaccines had been introduced in 96 countries.

TyVAC notes that obstacles due to cultural differences, inadequate financing, a poorly planned supply chain, healthcare worker skepticism, lack of parental support, and programmatic suitability can undermine new vaccine introduction if they are not considered and addressed in the planning phase prior to country introduction. To support successful uptake of TCV, TyVAC identifies concerns, expectations, and roles of ministry of health staff, parents, donors, and healthcare workers. For example, parents may have concerns about additional injections, safety, and the need for a new vaccine. The WHO, as well as global, regional, and national immunisation advisors and frontline immunisation providers, is aware that adding new vaccines potentially creates new challenges such as concerns about the administration of multiple injections during a vaccination visit. To address these concerns, TyVAC's broad-based plan integrates country-specific elements of A&C and health economics into engagement with ministries of health, immunisation technical advisory groups, national immunisation programmes, and other stakeholders.

Now that global policy recommendations are in place, the TyVAC focus is transitioning to creating messaging, identifying country champions, and hosting national, regional, and local events to connect with the larger typhoid and water, sanitation, and hygiene (WASH) communities. To generate broader support, TyVAC engages, collaborates, and partners with other organisations working on typhoid. In addition, TyVAC identifies opportunities to raise awareness of the global burden by tapping into existing conferences, campaigns, and partner publications to distribute materials, to blog, and to educate people about typhoid and TCVs. For example, TyVAC and the Coalition Against Typhoid created a broad call to action to "Take on Typhoid" (see Related Summaries, below). The initiative, which engages a diverse group of stakeholders, centres around a website offering advocacy tools, data, and relevant information to ensure partners are informed, empowered, and ready to fight for global, regional, and national prioritisation of integrated typhoid control solutions. Resources provide answers to questions, equip champions with data and evidence, and support advocacy for stronger WASH and TCV programmes.

In conclusion: "The TyVAC framework of evidence to support TCV introduction, global policy recommendations and financing, country willingness and readiness to introduce, local uptake and sustainability, and adequate, stable supply of affordable vaccine highlights broad components of vaccine introduction used to navigate the intricate process of TCV introduction. Understanding this complexity, level of detail, and uniqueness is critical to accelerating vaccine introduction."